| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
BMS-983970 targets the Notch signaling pathway by inhibiting gamma-secretase, the enzyme responsible for cleaving Notch receptors and releasing the intracellular domain that drives transcriptional activation. As a pan-Notch inhibitor, it blocks signaling through all four Notch receptors (Notch1–4).
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| ln Vitro |
BMS-983970 inhibits Notch signaling and demonstrates anti-tumor activity in preclinical models. In T-cell acute lymphoblastic leukemia (T-ALL) and solid tumor xenograft models, the compound shows anti-tumor efficacy. Detailed in vitro IC50 values for Notch inhibition have been characterized in cell-based reporter assays.
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| ln Vivo |
In solid tumor xenograft models and T-cell acute lymphoblastic leukemia (T-ALL) models, BMS-983970 demonstrates anti-tumor efficacy [1].
BMS-983970 demonstrates anti-tumor activity in T-cell acute lymphoblastic leukemia (T-ALL) and solid tumor xenograft models. The compound's oral bioavailability and pan-Notch inhibitory activity make it a promising therapeutic for Notch-driven malignancies. Efficacy has been shown in multiple preclinical tumor models. |
| Enzyme Assay |
Cell-free assays for BMS-983970 utilize purified gamma-secretase enzyme complex and a Notch-derived peptide substrate. The cleavage reaction is performed in the presence of increasing concentrations of the compound. Cleavage products are quantified by fluorescence or mass spectrometry. IC50 values are determined from concentration-response curves. Alternatively, Notch signaling can be assessed in cell-based reporter assays.
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| Cell Assay |
Cells expressing Notch receptors (e.g., T-ALL cell lines) are treated with BMS-983970 at various concentrations. Notch target gene expression (e.g., Hes1, Hey1) is assessed by qRT-PCR. Notch intracellular domain levels are measured by Western blot. Cell proliferation, viability, and apoptosis assays are performed to evaluate anti-tumor activity. The compound's effects on cell cycle and differentiation can also be assessed.
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| Animal Protocol |
In vivo animal studies for BMS-983970 are conducted in mouse xenograft models of T-ALL and solid tumors. The compound is administered orally (p.o.) at various doses. Tumor growth is measured over time, and tumor regression or growth inhibition is calculated. Pharmacodynamic markers (Notch target gene expression in tumor tissue) are assessed. Body weight and clinical signs are monitored for tolerability.
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| ADME/Pharmacokinetics |
BMS-983970 is orally bioavailable. As a small molecule (MW 518.5, formula C26H26F4N4O3), it has favorable drug-like properties for oral administration. Detailed PK parameters including Tmax, half-life, clearance, volume of distribution, and oral bioavailability have been characterized in preclinical species. The compound is metabolized primarily via hepatic pathways.
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| Toxicity/Toxicokinetics |
Toxicity data for BMS-983970 from preclinical studies indicate that pan-Notch inhibition can cause gastrointestinal and other toxicities due to the essential role of Notch signaling in intestinal homeostasis and other tissues. Standard genotoxicity, reproductive toxicity, and chronic toxicity studies have been conducted to support clinical development. The therapeutic window is defined by the balance between anti-tumor efficacy and on-target toxicity.
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| References | |
| Additional Infomation |
BMS-983970 (molecular formula C26H26F4N4O3, MW 518.5) is an oral pan-Notch inhibitor developed by Bristol-Myers Squibb for the treatment of multiple cancers. It demonstrates anti-tumor activity in T-cell acute lymphoblastic leukemia and solid tumor xenograft models. The compound represents a therapeutic strategy for Notch-driven malignancies.
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| Molecular Formula |
C26H26F4N4O3
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|---|---|
| Molecular Weight |
518.50
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| Exact Mass |
518.194
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| CAS # |
1584713-87-0
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| PubChem CID |
73388374
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
37
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| Complexity |
886
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC(C([H])([H])C([H])([H])[C@@]([H])(C(N([H])[C@]1([H])C(N([H])C2C(=C([H])C([H])=C([H])C=2C(C2C([H])=C([H])C([H])=C([H])C=2[H])=N1)F)=O)=O)[C@@]([H])(C(N([H])[H])=O)C([H])([H])C1([H])C([H])([H])C1([H])[H])(F)F
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| InChi Key |
RANYIWAZSQWERN-WLENULPWSA-N
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| InChi Code |
InChI=1S/C26H26F4N4O3/c27-19-8-4-7-17-20(15-5-2-1-3-6-15)32-23(25(37)33-21(17)19)34-24(36)16(11-12-26(28,29)30)18(22(31)35)13-14-9-10-14/h1-8,14,16,18,23H,9-13H2,(H2,31,35)(H,33,37)(H,34,36)/t16-,18+,23-/m1/s1
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| Chemical Name |
(2R,3S)-3-(cyclopropylmethyl)-N1-((S)-9-fluoro-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2-(3,3,3-trifluoropropyl)succinamide
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| Synonyms |
BMS-983970; BMS 983970; BMS983970.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~96.43 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9286 mL | 9.6432 mL | 19.2864 mL | |
| 5 mM | 0.3857 mL | 1.9286 mL | 3.8573 mL | |
| 10 mM | 0.1929 mL | 0.9643 mL | 1.9286 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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